Chemical hemorrhagic cystitis: Diagnostic and therapeutic pitfalls (Review) (original) (raw)
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Chemical- and radiation-induced haemorrhagic cystitis: current treatments and challenges
BJU International, 2013
Review therefore, the exact prevalence is unknown. Treatment can be problematic, especially in elderly patients who may be frail and have comorbidities [4], and because the condition often responds inadequately to the usual symptomatic therapies. In severe cases, HC is associated with significant morbidity, prolonged hospitalisation and occasional mortality, and may require more aggressive measures, e.g. supravesical urinary diversion, vesical artery selective embolization, and cystectomy [5]. Furthermore, as the global burden of cancer is forecast to rise, primarily due to ageing and growth of the world's population [6], it is likely that the incidence of HC will rise too because of the increasing use of RT and chemotherapy. However, there is currently a lack of consensus about the best treatment for patients with chemical-and RT-induced HC, as well as a lack of UK-led guidelines available on how it should optimally be defined and managed. The aim of the present article is to review the predisposing risk factors for chemical-and RT-induced HC and the evidence for the different therapeutic and preventive measures that have been used to help clinicians better manage this potentially disabling condition. Methods A comprehensive literature search was undertaken in PubMed to retrieve studies and case reports, published in English, relating to the treatment of chemical-and RT-induced HC from 1980 to September 2012. The search was conducted using a comprehensive search strategy, including the terms 'haemorrhagic cystitis' , 'chemical cystitis' , 'radiation cystitis' in combination with 'risk factors' , 'chemotherapeutic drugs' , 'hyaluronic acid' , 'sodium hyaluronate' , 'hyperbaric oxygen' , 'mesna' , 'hyperhydration' , 'bladder irrigation' , 'pentosanpolysulphate' , 'oestrogen' , 'recombinant factor VII' , 'formalin' , and 'prostaglandin'. The search results were supplemented by review of the bibliographies of key articles for additional studies, inclusion of relevant abstracts presented at key meetings, as well as expert input, to help ensure the capture of all pertinent data.
Guidelines for the diagnosis, prevention and management of chemical- and radiation-induced cystitis
Journal of Clinical Urology, 2014
Objective Haemorrhagic cystitis (HC) is a relatively common complication of chemotherapy and radiotherapy to the pelvic area, but can be a challenging condition to treat, particularly since there is currently a lack of UK-led guidelines available on how it should optimally be defined and managed. Materials and methods A comprehensive literature search was undertaken to evaluate the evidence for the diagnosis, prevention and management of cancer treatment-induced HC. Results Recommendations and a proposed management algorithm for the diagnosis, prevention and treatment of HC, as well as the management of intractable haematuria, have been developed based on the expert opinion of the multidisciplinary consensus panel following a comprehensive review of the available clinical data. Conclusion These guidelines are relevant and applicable to current clinical practice and will help clinicians optimally define and manage this potentially serious condition.
Prevention and treatment of cyclophosphamide and ifosfamide-induced hemorrhagic cystitis
Journal of Molecular Pathophysiology, 2012
Free radicals and non-radical reactive molecules as well as several cytokines (e.g. tumor necrosis factor-α and interleukin family) and transcription factors (e.g. nuclear factor-κB and activator protein-1) are now known to take part in the pathogenesis of cyclophosphamide (CP) and ifosfamide (IF) induced hemorrhagic cystitis (HC). When these molecular factors are taken into account pathogenesis of bladder toxicity can be summarized in three steps: (1) acrolein rapidly enters into the uroepithelial cells, (2) activates intracellular ROS and NO production (directly or through transcription factors) leading to peroxynitrite production, and (3) finally the elevated peroxynitrite level basically damages lipids (lipid peroxidation), proteins (protein oxidation) and DNA (strand breaks) leading to PARP activation, a DNA repair enzyme. DNA damage causes PARP overactivation, resulting in the depletion of oxidized nicotinamide adenine dinucleotide (NAD+) and adenosine triphosphate (ATP), and consequently in necrotic cell death. There is no doubt that for an effective prevention against CP-and IF-cystitis all pathophysiological mechanisms must be taken into consideration. Experimental works reporting beneficial effects of antioxidants, iNOS inhibitors, cytokine blockers or hyperbaric oxygen (HBO) treatment, against CP-and/or IF-induced HC exist in literature. In this article, we discussed the possible mechanisms and effectiveness of agents used in addition to mesna to prevent CP-and IF-cystitis. In conclusion, antioxidants, iNOS inhibitors, peroxynitrite scavengers, anti-inflammatory agents, as well as HBO therapy may be added to mesna administration in clinical trials in order to obtain the best protocol to improve quality of patients comfort
Background and Aim: Hemorrhagic cystitis (HC) is an inflammation of the urinary bladder defined by signs of urinary bladder irritation and hematuria. It is thought that damage to the Glycosaminoglycan-(GAG) layer, which coats the uroepithelium and provides the initial barrier for physiological protection, may be the first step in its development. The disease can be triggered by chemotherapeutic drugs exposure and radiation therapy. The incidence rate of HC is predicted to rise substantially in the future as more aggressive treatments of cancer are implemented.
Indian Journal of Cancer, 2006
BACKGROUND: Hemorrhagic cystitis (HC) is a dose limiting side effect of cyclophosphamide (CYP). AIM: In this study, we aimed to investigate the role of amifostine in the protection of CYP-induced HC and compare its efficacy with mesna. SETTING AND DESIGN: This animal study was conducted in the Experimental Animals Breeding and Research Center of the Medical Faculty of Uludag University. MATERIALS AND METHODS: Male Wistar rats (150-200 g; 10 rats per group) were randomly assigned to four groups. Group I (control group) received no drugs, group II received CYP (200 mg/kg, i.p.) alone, group III received amifostine (200 mg/kg, i.p.) and CYP, and group IV received CYP and mesna (40 mg/kg, i.p.) immediately and 4 and 8 h after administration of CYP. Bladders of animals were assessed macroscopically and histologically 24 h later. Gross assessment for presence of edema and hemorrhage and histological evaluation of damage to the bladder were scored according to Gray's criteria. STATISTICAL ANALYSIS USED: For macroscopic and microscopic data, we used statistical evaluation by Kruskal-Wallis nonparametric analysis of variance followed by the Mann-Whitney U-test. RESULTS: All the animals in group II had evidence of HC. Significant histological damage and macroscopic changes were present in this group compared to control group (P<0.001). The median scores for bladder damage in group III and IV were significantly lower compared to group II (P<0.001). When the median scores for bladder damage of group I, III, and IV were compared, there was no significant difference among these groups. CONCLUSION: This study demonstrated the efficacy of amifostine in prevention of cyclophosphamide-induced hemorrhagic cystitis.
Demographic, Clinical, and Treatment Parameters Influencing the Outcome of Acute Cystitis
Clinical Infectious Diseases, 1999
A meta-analysis of six double-blinded clinical trials was undertaken to identify risk factors associated with bacteriologic outcome in 3,108 women with acute cystitis. Eleven antibiotic regimens were used, including ciprofloxacin, ofloxacin, norfloxacin, trimethoprim-sulfamethoxazole, and nitrofurantoin. Entry criteria for all studies were identical. Among 2,409 patients who were defined to be valid for efficacy analysis, pathogens included Escherichia coli (78.6%), Staphylococcus saprophyticus (4.4%), Klebsiella pneumoniae (4.3%), Proteus mirabilis (3.7%), and "other" (9%). Causative bacteria were eradicated at the end of treatment in 93% of patients. The following parameters were associated with successful bacteriologic outcome: not using a diaphragm (P ؍ .0041), treatment for 3 days (P ؍ .0043), pathogen not "other" (P ؍ .0043), symptom duration of <2 days (P ؍ .0096), and African American race (P ؍ .0147). K. pneumoniae (P ؍ .0496) and "other" pathogens (P ؍ .0018) were associated with increased probability of bacteriologic treatment failure. The presence of pyuria (10 WBCs per high-power field) did not correlate with outcome and was inversely correlated with the finding of 10 5 bacterial colony-forming units per mL of urine (P < .001). This large database identifies new parameters associated with treatment outcomes of acute cystitis and calls into question current clinical trial guidelines.
Journal of Urology, 1997
The aim of this research was to compare the protective effects of mesna, hyperbaric oxygenation (HBO), and their combination in cyclophosphamide-induced hemorrhagic cystitis in guinea pigs. Following one dose of i.p. 21.5 mg./kg. mesna administration 20 minutes before i.p. 68.1 mg./kg. cyclophosphamide, 3 additional doses of mesna were given every three hours. A total of 8 HBO exposures, 5 of which were applied prophylactically before cyclophosphamide, were performed at 2.8 ATA for 90 minutes 2 times a day. Although mesna or HBO provided significant protection for cyclophosphamide-cystitis in animal bladders, there was also significant damage compared with controls. The combination of mesna and HBO, which act through independent mechanisms, resulted in complete protection, since mean histological scores and hematuria levels in this group were not different from controls (p >0.05). Therefore, this combination may be a useful tool in the prophylaxis and treatment of cyclophosphamide-induced hemorrhagic cystitis.